Quaternary ammonium salts of aromatic amine compounds, their preparation and pharmaceutical compositions in which they are present

Abstract

The present invention relates to quaternary ammonium salts of the formula ##STR1## in which: J is either a group Ar--CXX'--CX" or a group Ar--(CH 2 ) x CH 1 , in which: Ar is a substituted or unsubstituted phenyl, a cycloalkyl, a pyridyl or a thienyl; X is hydrogen; X' is hydrogen or is combined with X" below to form a carbon-carbon bond, or else X and X' together form an oxo group; X" is hydrogen or forms a carbon-carbon bond with X'; X is zero or one; and X 1 is hydrogen (n=0), a hydroxyl, an alkoxy, an acyloxy, a carboxyl, a carbalkoxy, a cyano or an alkoxyamino group; Q is an alkyl group or a benzyl group; A⊖ is an anion; m is 2 or 3; Ar', R, T and Z are as defined in the specification, are neurokinin receptor antagonists.

What is claimed is: 
     
       1. A quaternary ammonium salt of the formula ##STR127## in which: J is *--either a group ##STR128## in which: Ar is a phenyl which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from: hydrogen, a halogen atom, a hydroxyl, a C 1  -C 3  -alkoxy, a C 1  -C 3  -alkyl and a trifluoromethyl, said substituents being identical or different; a C 3  -C 7  -cycloalkyl group; a pyridyl group; or a thienyl group;   X is hydrogen;   X' is hydrogen or is combined with X" below to form a carbon-carbon bond, or else X and X' together form an oxo group; and   X" is hydrogen or forms a carbon-carbon bond with X'; *--or a group ##STR129## in which: Ar is as defined above;     x is zero or one; and   X 1  is hydrogen, only when x is zero; a hydroxyl; a C 1  -C 4  -alkoxy; a C 1  -C 4  -acyloxy; a carboxyl; a C 1  -C 4  -carbalkoxy; a cyano; a group --NH--CO--Alk in which Alk is a C 1  -C 6  -alkyl; a mercapto group; or a C 1  -C 6  -alkylthio group; or else X 1  forms a double bond with the carbon atom to which it is bonded and with the adjacent carbon atom in the piperidine;   Q is a C 1  -C 6  -alkyl group or a benzyl group;   A⊖ is an anion selected from chloride, bromide, iodide, acetate, methanesulfonate and paratoluenesulfonate;   m is 2 or 3;   Ar' is a phenyl which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from: hydrogen, a halogen atom, preferably a chlorine or fluorine atom, a trifluoromethyl, a C 1  -C 4  -alkoxy and a C 1  -C 4  -alkyl, said substituents being identical or different; a thienyl; a benzothienyl; naphthyl; or an indolyl optionally N-substituted by a C 1  -C 4  -alkyl;   R is hydrogen or a C 1  -C 6  -alkyl;   T is a group selected from: ##STR130## W being an oxygen or sulfur atom; and Z is hydrogen, M or OM when T is the group ##STR131## or M when T is the group ##STR132## M being a C 1  -C 6  -alkyl ; an α-hydroxybenzyl, an α-hydroxybenzylalkyl or phenylalkyl in which the alkyl is C 1  -C 3  and which is unsubstituted or mono-substituted or polysubstituted on the aromatic ring by a halogen, a trifluoromethyl, a C 1  -C 4  -alkyl, a hydroxyl or a C 1  -C 4  -alkoxy; a pyridylalkyl in which the alkyl is C 1  -C 3  ; a naphtylalkyl in which the alkyl is C 1  -C 3  and which is unsubstituted or substituted on the naphthyl ring by a halogen, a trifluoromethyl, a C 1  -C 4  -alkyl, a hydroxyl or a C 1  -C 4  -alkoxy; a pyridylthioalkyl in which the alkyl is C 1  -C 3  ; a styryl; or a subsituted or unsubstituted mono-, di or tri-cyclic aromatic or heteroaromatic group.   
     
     
       2. A compound according to claim 1 of formula (I) in which Z is naphthyl, benzyl, α-hydroxybenzyl or phenyl which are unsubstituted or substituted by a substituent selected from chlorine or fluorine and C 1  -C 4  -alkyl or -alkoxy. 
     
     
       3. A compound according to claim 2 of formula (I) in which R is hydrogen or methyl, Ar' is 3,4-dichlorophenyl, and T is carbonyl. 
     
     
       4. 1- 3-(3,4-Dichlorophenyl)-4-(N-methyl-3-isopropoxyphenylacetylamino)butyl!-4-phenyl-N(a)-methyl-1-piperidinium iodide, a compound according to claim 1. 
     
     
       5. 1- 3-(3,4-Dichlorophenyl)-4-(N-methyl-3-isopropoxyphenylacetylamino)butyl!-4-phenyl-N(e)-methyl-1-piperidinium iodide, a compound according to claim 1. 
     
     
       6. 1- 3-(3,4-Dichlorophenyl)-4-(N-methyl-α-hydroxyphenylacetamido)butyl!-4-phenyl-N(a)-methyl-1-piperidinium iodide, a compound according to claim 1. 
     
     
       7. A pharmaceutical composition which comprises a compound according to claim 1, and a pharmaceutically acceptable excipient. 
     
     
       8. A pharmaceutical composition according to claim 7 in the form of a dosage unit.